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. 2018 Jul 6;20(13):3988-3991.
doi: 10.1021/acs.orglett.8b01561. Epub 2018 Jun 15.

Hexafluoroisopropanol as the Acid Component in the Passerini Reaction: One-Pot Access to β-Amino Alcohols

Jordy M Saya  1 , Rayan Berabez  1 , Pim Broersen  1 , Imme Schuringa  1 , Art Kruithof  1 , Romano V A Orru  1 , Eelco Ruijter  1
Affiliations

Hexafluoroisopropanol as the Acid Component in the Passerini Reaction: One-Pot Access to β-Amino Alcohols

Jordy M Saya et al. Org Lett. .

Abstract

A new Passerini-type reaction in which hexafluoroisopropanol functions as the acid component is reported. The reaction tolerates a broad range of isocyanides and aldehydes, and the formed imidates can be reduced toward β-amino alcohols under mild and metal-free conditions. In addition, the imidate products were shown to undergo an unprecedented retro-Passerini-type reaction under microwave conditions, providing valuable mechanistic information about the Passerini reaction and its variations.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Novel Passerini-Type Reactions
Scheme 2
Scheme 2. Scope of the Passerini-Type Reaction,
Standard conditions: isocyanide (1 mmol), aldehyde (1.3 mmol), HFIP (3 mmol) in CH2Cl2 (1 M), rt. Isolated yields. HFIP (0.1 M) was used as the solvent.
Scheme 3
Scheme 3. Scope of the One-Pot β-Amino Alcohol Synthesis,
Standard conditions: isocyanide (1 mmol), aldehyde (1.3 mmol), HFIP (3 mmol) in CH2Cl2 (1 M), rt, next diluted with HFIP (0.1 M), then BH3·NH3 (3 mmol) and TFA (5 mmol). Isolated yields. No TFA.
Scheme 4
Scheme 4. Synthesis of Propranolol and (±)-Rivaroxaban
Scheme 5
Scheme 5. Concerted Mechanism of the Passerini Reaction
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